Dentifrice formulation and method of treating teeth, mouth and throat therewith to reduce plaque accumulation and irritation

ABSTRACT

Dentifrice formulations containing monoalkyl and dialkyl ethers of dianhydrohexitols in the form of toothpaste, mouthwash, chewing gums, confections, toothpicks and dental floss are effective in the treatment of oral surfaces and cavities to reduce irritation and plaque accumulation caused by the action of bacteria.

This is a divisional of co-pending application Ser. No. 685,167, filedon Dec. 21, 1984, now U.S. Pat. No. 4,585,649.

The present invention relates to the treatment of the mouth and throatto reduce irritation and plaque accumulation caused by the action ofbacteria. It is particularly related to dentifrice formulations in theform of toothpaste, gels, mouthwash, chewing gums, and confectionshaving therapeutic and prophylactic action.

It is widely recognized that regular use of antimicrobial dentifricecombinations may significantly reduce the buildup of plaque on teeth.Plaque is the attachment of microorganisms to the pellicle which coatsteeth and tongue cavities and forms a surface upon which furtheraccumulation may grow to form hard calculus deposits. If not removed,these deposits cause inflammation of the supportive tissues of theteeth. The ensuing carious lesions account for most of the periodontaldisease which may result in loosening and eventual loss of teeth.

While the mechanism for the formation of plaque remains speculative, itis generally recognized that foods containing natural sugars such assucrose and glucose are consumed by plaque forming organisms such asStreptococcus mutans. Dental decay is thought to be initiated bydecalcification of dental enamel by the organic acids which are producedby fermentative catabolism of sugars by bacteria such as S. mutans GS-5.The by-product calculus which forms between the teeth and gums is themajor cause of gingivitis which is the inflammatory action which resultsin swelling, redness, cellular exudate and bacterial growth.

The only effective method known to control the mal effects of plaque inthe mouth is mechanical removal. Daily brushing, flossing and irrigationusing a toothbrush, toothpick, dental floss and water picks areeffective in retarding the formation of caries and gum diseases. Suchtreatment if carried out improperly over long periods of time alsocauses damage to the gums by the abrasive action of brush bristles,floss and picks. Tooth erosion may be caused by the abrasives usuallycontained in conventional toothpaste.

In its broadest description the present invention is directed to amethod of removing and reducing the formation of plaque and calculus inthe oral cavity. The invention also provides for dentifrice compositionsuseful in reducing and removing plaque from the mouth surfaces andresultant irritation caused by plaque formation. It is furthercontemplated that the invention includes a method for treating thethroat to relieve irritation.

Specifically, the invention involves a method for relieving throatirritations and inhibiting the formation of plaque and calculus whichcomprises regularly treating the surfaces of the teeth, mouth, gums andthroat of mammals with a composition containing an effective amount of amonoalkyl or dialkyl isohexide having the general formula: ##STR1##wherein R' and R" may be individually selected from the group consistingof --CH₃, --C₂ H₅, --C₃ H₇, --C₄ H₉ and alternatively --H when the otherR' or R" is an alkyl group of 1-4 carbon atoms. The invention alsoincludes a dentifrice, gum, or confection which contains as an essentialingredient a compound of Formula I. The invention further includes amethod for inhibiting the proliferation of bacteria especially S-mutansin the mouth by contacting the surfaces of the mouth with a prophylacticamount of a compound of Formula I.

The essential compounds used in the practice of the invention aremonoalkyl and dialkyl ethers of 1,4,3,6-dianhydrohexitols of D-glucitol,D-mannitol, and L-iditol. These compounds are also referred to as monoand dialkyl ethers of isosorbide, isomannide and isoidide. For example,preparations of essentially pure dimethylisosorbide (DMI) may contain 1to 2% by weight dimethyl isomannide, 1-2% by weight dimethyl isoidide,and 1-2% by weight of the monomethyl equivalents.

The compounds of the invention specifically include methylisosorbide,dimethylisosorbide, ehtylisosorbide, diethylisosorbide (DEI),propylisosorbide, dipropylisosorbide, monoisopropylisosorbide,diisopropylisosorbide (DIPI), methylethylisosorbide,methylpropylisosorbide, ethylpropylisosorbide, butylisosorbide,dibutylisosorbide, isobutylisosorbide, diisobutylisosorbide,methylbutylisosorbide, ethylbutylisosorbide, propylbutylisosorbide, andthe equivalent isomannide and isoidide modifications.

These compounds are conveniently made by the conventional Williamsonether synthesis technique and modifications thereof wherein adianhydrohexitol is reacted with an alkyl halide or sulfate, or amixture of alkyl halides or sulfates, in strong alkali followed byconventional purification and distillation techniques.Dimethylisosorbide is commercially available.

The tetraether compounds are usually obtainable as clear water whiteliquids having a pleasant odor and mouthfeel. Aqueous dilutions are aseffective as pure liquids when applied to teeth. Dimethylisosorbide isconsidered non-toxic and is considered to be neither a primary irritantto human skin nor a skin sensitizer. In vivo testing withdimethylisosorbide at 100%, 80%, 50%, 25% and 10% aqueous solutions intoothdrops, toothpaste and mouthwash has produced no contraindications.

Dentifrice formulations containing the materials of Formula I may be inthe form of a toothpaste, toothpaste gel, toothdrops, mouthwash, gargle,chewing gum, hard candy and soft candy. These formulations may containfrom 5 to 95% by weight of the compounds of Formula I and at least twoadditional ingredients to improve taste, mouthfeel and effectiveness asa prophylactic. Such ingredients include water, solvents, stabilizers,coloring agents, flavoring agents, medicaments, astringents, detergents,polishing agents, sweeteners, gelling agents, thickeners, pigments andother antibacterial agents. Such combinations may be in the form of athin liquid, paste, gel or taffy, supported on a solid particulate,(e.g., sugar or granular mannitol), wood (e.g., toothpicks), string(e.g., such as the type used in dental floss) or masticatory substances.

Mouthwashes and gargles are effective at concentrations of 5-90% byweight of the Formula I compounds in aqueous or alcoholic solution orother suitable liquid. Any usable liquid formulation containing thecompound of Formula I for bathing, rinsing or gargling the tissues ofthe mouth or throat without injury is included within the scope of theinvention. The formulations may include such other agents as propyleneglycol, glycerine, ethylenediaminetetracetic acid, methylparaben,detergents, coloring agents and flavors. Of course, the formulation mayinclude other well known astringents and medicaments such as solublesalts including the ascorbates, citrates, tartrates, chlorides,fluorides, bromides, sulfates, and phosphates of metals selected fromsodium, potassium, lithium, magnesium and calcium. Popular flavorsinclude peppermint, wintergreen, orange, lime, cherry, strawberry,cinnamon, clove, anise and the like. Appropriate coloring agents may beadded e.g., to match the flavor.

Typical formulations are illustrated but not limited to those of thefollowing examples wherein all proportions are in parts by weight unlessotherwise specified. Abbreviations used have their customary meanings.

In Examples 1-30 it should be understood that the proportions ofingredients shown at the left column is the same for column examples tothe right in each Table unless otherwise specified.

                                      TABLE I                                     __________________________________________________________________________    Examples 1-5                                                                                1       2      3      4      5                                                     Wt.    Wt.    Wt.    Wt.    Wt.                            Ingredients   Wt/g %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %                              __________________________________________________________________________    Water (Distilled)                                                                           1400    1400   1100   600     0                                 Sodium Benzoate USP                                                                         4                                                               Saccharin, Sodium USP                                                                       50                                                              Citric Acid (Anhydrous                                                                      2                                                               Grade)                                                                        TWEEN ® 60 (Surfactant)                                                                 8                                                               Peppermint Oil (Fritzschi                                                                     3.4                                                           H-672)                                                                        Clove Oil USP (Amend)                                                                         .6                                                            Dimethylisosorbide                                                                          200  10%                                                                              100 5% 500 25 1000                                                                              50 1800                                                                              90%                            (Atlas G-100)                                                                 Ethyl Alcohol 200                           0                                 Green Color (0.5 g FD & C                                                                   2                                                               Green in 500 gm H.sub.2 O                                                     Water (distilled q.s.                                                                       130     230    130    130    130                                to 2000 mls.)                                                                 __________________________________________________________________________

                                      TABLE II                                    __________________________________________________________________________    Examples 6-10                                                                 MOUTHWASH                                                                                   6       7      8      9      10                                                    Wt.    Wt.    Wt.    Wt.    Wt.                            Ingredients   Wt/g %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %                              __________________________________________________________________________    Water (Distilled)                                                                           1400    1400   1100   600     0                                 Sodium Benzoate USP                                                                         4                                                               Saccharin, Sodium USP                                                                       50                                                              Citric Acid (Anhydrous                                                                      2                                                               Grade)                                                                        TWEEN ® 60 (Surfactant)                                                                 8                                                               Peppermint Oil (Fritzschi                                                                     3.4                                                           H-672)                                                                        Clove Oil USP (Amend)                                                                         .6                                                            Diethyl Isosorbide                                                                          200  10%                                                                              100 5% 500 25 1000                                                                              50 1800                                                                              90%                            Ethyl Alcohol 200                           0                                 Green Color (0.5 g FD & C                                                                   2                                                               Green in 500 gm H.sub.2 O                                                     Water (distilled q.s.                                                                       130     230    130    130    130                                to 2000 mls.)                                                                 __________________________________________________________________________

                                      TABLE III                                   __________________________________________________________________________    Examples 11-17                                                                MOUTHWASH                                                                                   11      12     13     14     15                                                    Wt.    Wt.    Wt.    Wt.    Wt.                            Ingredients   Wt/g %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %                              __________________________________________________________________________    Water (Distilled)                                                                           1400    1400   1100   600     0                                 Sodium Benzoate USP                                                                         4                                                               Saccharin, Sodium USP                                                                       50                                                              Citric Acid (Anhydrous                                                                      2                                                               Grade)                                                                        TWEEN ® 60 (Surfactant)                                                                 8                                                               Peppermint Oil (Fritzschi                                                                     3.4                                                           H-672)                                                                        Clove Oil USP (Amend)                                                                         .6                                                            Diisopropyl isosorbide                                                                      200  10%                                                                              100 5% 500 25 1000                                                                              50 1800                                                                              90%                            Ethyl Alcohol 200                           0                                 Green Color (0.5 g FD & C                                                                   2                                                               Green in 500 gm H.sub.2 O                                                     Water (distilled q.s.                                                                       130     230    130    130    130                                to 2000 mls.)                                                                 __________________________________________________________________________

                                      TABLE IV                                    __________________________________________________________________________    Examples 16-20                                                                MOUTHWASH                                                                                   16      17     18     19     20                                                    Wt.    Wt.    Wt.    Wt.    Wt.                            Ingredients   Wt/g %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %                              __________________________________________________________________________    Water (Distilled)                                                                           1400    1400   1100   600     0                                 Sodium Benzoate USP                                                                         4                                                               Saccharin, Sodium USP                                                                       50                                                              Citric Acid (Anhydrous                                                                      2                                                               Grade)                                                                        TWEEN ® 60 (Surfactant)                                                                 8                                                               Peppermint Oil (Fritzschi                                                                     3.4                                                           H-672)                                                                        Clove Oil USP (Amend)                                                                         .6                                                            Diisopropyl isosorbide                                                                      200  10%                                                                              100 5% 500 25 1000                                                                              50 1800                                                                              90%                            Ethyl alcohol 200                           0                                 Green Color (0.5 g FD & C                                                                   2                                                               Green in 500 gm H.sub.2 O                                                     Water (distilled q.s.                                                                       130     230    130    130    130                                to 2000 mls.)                                                                 __________________________________________________________________________

                                      TABLE V                                     __________________________________________________________________________    Examples 21-25                                                                MOUTHWASH                                                                                   21      22     23     24     25                                                    Wt.    Wt.    Wt.    Wt.    Wt.                            Ingredients   Wt/g %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %                              __________________________________________________________________________    Water (Distilled)                                                                           1400    1400   1100   600     0                                 Sodium Benzoate USP                                                                         4                                                               Saccharin, Sodium USP                                                                       50                                                              Citric Acid (Anhydrous                                                                      2                                                               Grade)                                                                        TWEEN ® 60 (Surfactant)                                                                 8                                                               Peppermint Oil (Fritzschi                                                                     3.4                                                           H-672)                                                                        Clove Oil USP (Amend)                                                                         .6                                                            Diisopropyl isosorbide                                                                      200  10%                                                                              100 5% 500 25 1000                                                                              50 1800                                                                              90%                            Ethyl Alcohol 200                           0                                 Green Color (0.5 g FD & C                                                                   2                                                               Green in 500 gm H.sub.2 O                                                     Water (distilled q.s.                                                                       130     230    130    130    130                                to 2000 mls.)                                                                 __________________________________________________________________________

                                      TABLE VI                                    __________________________________________________________________________    Examples 26-30                                                                MOUTHWASH                                                                                   26      27     28     29     30                                                    Wt.    Wt.    Wt.    Wt.    Wt.                            Ingredients   Wt/g %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %  Wt/g                                                                              %                              __________________________________________________________________________    Water (Distilled)                                                                           1400    1400   1100   600     0                                 Sodium Benzoate USP                                                                         4                                                               Saccharin, Sodium USP                                                                       50                                                              Citric Acid (Anhydrous                                                                      2                                                               Grade)                                                                        TWEEN ® 60 (Surfactant)                                                                 8                                                               Peppermint Oil (Fritzschi                                                                     3.4                                                           H-672)                                                                        Clove Oil USP (Amend)                                                                         .6                                                            Diisopropyl isosorbide                                                                      200  10%                                                                              100 5% 500 25 1000                                                                              50 1800                                                                              90%                            Ethyl Alcohol 200                           0                                 Green Color (0.5 g FD & C                                                                   2                                                               Green in 500 gm H.sub.2 O                                                     Water (distilled q.s.                                                                       130     230    130    130    130                                to 2000 mls.)                                                                 __________________________________________________________________________

The clear liquid mouthwash formula of Example 1 was used by five adultsubject volunteers for a period of three months at least two times aweek. Each reported a long lasting pleasing after-taste and mouthfeel.It was especially noticed that the tongue and teeth remained clean andfree of deposit for several hours after each use. The products ofExamples 2-30 are expected to provide equivalent performance.

Dental creams and gels are solutions of the compounds of Formula I whichare thickened to a desired consistency. They range from clear liquidsand free flowing gels having only thickener, color and flavor to a thickpaste having pigment, abrasives, thickeners, medicaments, flavors,colors, vehicles, preservatives, humectants, surfactants, detergents,antioxidants, salts, sweetening agents, polishing agents and the like.

Thickening agents include hydroxyethyl cellulose, hydroxymethylcellulose, synthetic gum, gum-like material such as Irish moss, gumtragocanth, xanthan, polyvinylpyrrolidone, starch polyvinylpolymers andfinely divided silicas such as silica aerosols.

Pigments include alumina, hydrated alumina, zirconia, titania, coloredlakes on alumina and titania, e.g., Red 2 G on alumina or FD and C Red19 on titania.

Surface active agents include such organic anionic, cationic, nonionicand ampholytic compounds to provide detersive and foaming action toachieve increased prophylactic action. These may be selected from fattyacid monoglycerides, monosulfate salts, salts of dodecyl benzenesulfonate, aliphatic acylamides, ethanolamine salts of fatty acids,ethyloxide/propyloxide polyether derivatives of polyol esters, polyetherderivatives of propylene diamine, and the like. The concentrations ofthese surfactants usually range from 0.05-5% by weight of thecomposition.

A variety of flavorings and/or sweeteners may be used in the paste orgel. Examples of flavoring oils include spearmint, peppermint,wintergreen, sassafras, clove, sage, anise, orange, eucalyptus, majoram,cinnamon, lemon, methylsalicylate and chloroform. Examples of sweetenersinclude sugar, lactose, maltose, maltitol, sorbitol, hydrogenated starchhydrolysates, sodium cyclamate, aspartame, perillartine, saccharine andcorn syrup. These additions are used in concentrations of 0.01-5% byweight.

Medications and treating agents to protect teeth from decay are used inconcentrations ranging from 0.01-1% by weight. Examples includefluorides of sodium, potassium, tin and sodium monofluorophosphate.

Typical antibacterial agents include N¹ -(4-chlorobenzyl)-N⁵-(2,4-dichlorobenzyl biguanide; p-chlorophenyl biguanide;4-chlorobenzhydril biguanide; 4-chlorobenzhydrilguanilurea;N-3-lauryloxypropyl-N⁵ -p-chlorobenzyl biguanide; similar knownantibacterial agents and their nontoxic acid addition salts.

EXAMPLES 31-45 Gelled Dentifrice

Gelled toothpaste was prepared in three lots (Examples 31-33) containing5%, 10% and 25% by weight dimethylisosorbide (DMI) by mixing 60, 120 and300 gram portions respectively of DMI with 20.4 gms peppermint oil, 3.6gms clove oil, 3 gms sodium saccharine, 2.4 gms sodium benzoate, 42 gmssodium hydroxypropyl cellulose thickener and water to make 1200 gms. Thegels were prepared by first mixing the selected amount of DMI, with thepeppermint oil and clove oil portions. To this mixture were added thewater, saccharine and sodium benzoate portions. The sodium hydroxypropylcellulose thickeners were added with vigorous stirring to form a smoothgel. The gel was then permitted to stand for about 24 hours andthereafter packaged into 1 ounce collapsible aluminum tubes for use.

Gel compositions of Examples 31-33, and pure 100% DMI were applied totoothbrushes by twelve adult volunteers labelled Subject A-L in TableVII and applied as they would normally in brushing (Examples 34-45). Inthe case of the 100% liquid several drops were placed on the brush. Thegelled compositions were easier to apply to the brush as expected. Ineach case moderate foaming occurred and is considered sufficient toprovide adequate removal of plaque and food particles which accumulate.In some cases the 100% DMI was considered too strong while anything lessthan 5% DMI was too mild. The most satisfactory results were obtained byusing 10-50% DMI in gels.

Each subject noticed an immediate improvement in mouth and teethfeel.Teeth were described as squeaky clean (the feeling obtained afterprofessional cleaning) after 2-3 days brushing and remained that way forthe duration of use. When test subjects resumed the use of commerciallyavailable toothpaste they noticed a return to a normal gritty film onthe teeth after 4 days or sooner. Two subjects brushed once and did notcontinue the test. Five subjects were examined professionally afterusing the DMI containing tooth cleaner. Very little plaque was noticed.Even the back molars which are difficult to reach with a brush remainedsubstantially free of plaque. In all cases gums appeared healthy.

A summary of testimonials given by the test subjects is outlined inTable VII wherein the first column indicates the age and sex of thesubjects, the remaining columns indicate the months of use, the DMIconcentration in the tooth cleaner and number of brushings per day(i.e., 100/2 means 100% DMI 2 times/day) and the last column lists thecomments.

                                      TABLE VII                                   __________________________________________________________________________    In Vivo Testing                                                               Examples 34-45                                                                               1                                                                             % DMI/No.                                                                            Month Number                                            Example                                                                            Subject                                                                           M/F-Age                                                                             Wash/Day                                                                             2  3    4  5  6  7  8  Comments*                        __________________________________________________________________________    34   A   M/59  100/2  50/2                                                                              25/2                                                                              10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             A, B, E                          35   B    F/55 100/2  100/2                                                                             10/2                                                                              10/2                                                                             10/2                                                                             10/2                                                                             10/2  A, B, E                          36   C   M/56  100/2  100/2                                                                             100/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             A, B, E                          37   D    F/25 100/2  100/2                                                                             100/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             A, B, E                          38   E   M/30  100/2  100/2                                                                             100/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             A, B, E                          39   F   M/50  100/2  100/2                                                                             100/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             10/2                                                                             A, B, E                          40   G    F/49  10/2  10/2                                                                              10/2                                                                              10/2           A, B, E                          41   H   M/50   10/2  10/2                                                                              10/2                                                                              10/2           A, B, E                          42   I   M/47   25/2  25/2                                                                              25/2                                                                              25/2           C, D                             43   J   M/51   10/2  10/2                   A, B, E                          44   K   M/45   10/2  10/2                                                                              10/2               A, B, E                          45   L   M/45   10/2                         A, B, E                          __________________________________________________________________________     *Comments                                                                     A -- Reduce plaque                                                            B -- Gums healthy                                                             C -- Gum bleeding stopped                                                     D -- Typical heavy plaque former: Problem reduced to normal to light          formation.                                                                    E -- Tongue feels clean                                                  

EXAMPLE 46-48 Tooth Cleaning Drops

    ______________________________________                                                      46       47     48                                              Ingredient      (% by Wt.)                                                    ______________________________________                                        Dimethylisosorbide                                                                            10         25     50                                          Peppermint Oil NF                                                                             1.5        1.5    1.5                                         Clove Oil NF    0.3        0.3    0.3                                         Sodium Saccharine NF                                                                          0.2        0.2    0.2                                         Sodium Benzoate NF                                                                            0.2        0.2    0.2                                         Water (distilled)                                                             q.s. to 100                                                                   ______________________________________                                    

Tooth cleaning drops were made by first dissolving the flavor oils indimethylisosorbide, second dissolving the sodium salts in half therequired water, third mixing the two portions and then adding water tofull weight of 100 gms.

Additional formulations containing 5 and 90% DMI were considered tooweak or too strong by some test subjects, however, even they appeared tobe effective. Other formulation Examples 49-56 are presented with otheractive compounds of Formula I. Each active is combined with theadditives as shown at the top of the left column in preparationindicated.

    ______________________________________                                        Examples 49-56                                                                Tooth Cleaning Solution                                                                  Exam- (% by Wt.)                                                   Ingredients  ple No. 49    50  51  52  53  54  55  56                         ______________________________________                                        Peppermint Oil NF                                                                          1.5                                                              Clove Oil NF .3                                                               Sodium Saccharin NF                                                                        0.2                                                              Sodium Benzoate NF                                                                         0.2                                                              Water (Distilled)                                                             q.s. to 100                                                                   Active                                                                        Diethylisosorbide    10                                                       Diisopropylisosorbide      5                                                  Methylethylisosorbide          25                                             Monomethylisosorbide               75                                         Monobutylisosorbide                    85                                     Dibutylisosorbide                          15                                 Dimethylisosorbide                             90                             Monomethylisosorbide                               95                         ______________________________________                                    

EXAMPLES 57-59 Conventional Toothpaste

    ______________________________________                                                         57     58     59                                             Ingredients        Parts by Wt.                                               ______________________________________                                        Dimethylisosorbide (DMI)                                                                         10       25     50                                         Cellulose gum, CMC-7MF                                                                           1.25     1.25   1.25                                       Glycerine          5.0      5.0    5.0                                        Magnesium Aluminum silicate                                                                      0.25     0.25   0.25                                       70% Sorbitol Solution USP                                                                        30.0     30.0   30.0                                       Dicalcium phosphate                                                                              28.0     28.0   28.0                                       dihydrate                                                                     Dicalcium phosphate                                                                              20.0     20.0   20.0                                       (Anhydrous)                                                                   Sodium Lauryl Sulfate                                                                            1.0      1.0    1.0                                        Sodium Saccharine  0.2      0.2    0.2                                        Flavor             q.s.     q.s.   q.s.                                       Water              q.s.     q.s.   q.s.                                       ______________________________________                                    

To make a conventional toothpaste the above quantity of cellulose gum isdispersed in glycerine. The magnesium aluminum sulfate is dispersed inwater under high shear. These two components are mixed with the DMI andsorbitol solution and thereafter with the remaining ingredients listedabove. Water is then added in a conventional mixer to obtain the desiredpaste viscosity. Fluoride salts may be added to the formulation forprevention of caries. Concentrations as low as 5% of DMI in such pasteformulations are effective. Similar concentrations of Formula Icompounds such as diethyl-, diisopropyl-, dibutyl-, methylbutyl-, ormonobutyl isosorbide may be employed with equivalent effectiveness andmay be incorporated into many equivalent opaque and clear gelformulations.

EXAMPLE 60 Clear Gel Toothpaste

    ______________________________________                                        Ingredients          % by Wt.                                                 ______________________________________                                        Dimethylisosorbide   10                                                       Cellulose gum CMC-9M31XF                                                                           0.3                                                      Glycerine            3                                                        70% Sorbitol/water solution USP                                                                    30                                                       Water                .3                                                       Sodium benzoate      .2                                                       Sodium saccharine    .2                                                       70% Sorbitol/water solution USP                                                                    30                                                       Polyethylene glycol 1540                                                                           5.0                                                      Hydrated silica (Syloid ® B-30)                                                                14.0                                                     Hydrated silica (Syloid ® 244)                                                                 8.5                                                      Flavor               q.s.                                                     70% Sorbitol/water solution USP                                                                    6.0                                                      Sodium lauryl sulfate                                                                              1.5                                                      ______________________________________                                    

Clear gel formulations may be made by adding the above-listedingredients together as follows:

Disperse cellulose gum in glycerin, blend 30.2 g. sorbitol, water,dimethylisosorbide, sodium benzoate, sodium saccharine and mix into auniform dispersion to form a first portion. Mix 30 g. of sorbitol withthe polyethylene glycol 1540 using moderate heat and agitation. Add thismixture to the first portion and stir until uniform consistency.

Dry blend the silicas. Using a Hobart type mixer or equivalent and addthe previously mixed materials. When a smooth gel develops add flavors,additional sorbitol and sodium lauryl sulfate.

Blend the mixture with minimum agitation until uniform consistency.Condition the resulting gel overnight at 50° C. Heat to 65° C. anddeaerate under vacuum. A Versator (Cornell Machine Company) orequivalent apparatus effectively deaerates this gel system.

EXAMPLES 61-64 Nonabrasive Toothpaste Gel

    ______________________________________                                        Ingredients (% by wt.)                                                                          61     62       63  64                                      ______________________________________                                        Peppermint Oil NF 1.5                                                         Clove Oil NF      .3                                                          Sodium saccharin NF                                                                             .2                                                          Sodium benzoate NF                                                                              .2                                                          Klucel MF Thickener                                                                             2.5                                                         (cellulose polymer)                                                           Sodium lauryl sulfate                                                                           1.5                                                         Water q.s.        100                                                         Dimethylisosorbide                                                                               10                                                         Diethylisosorbide        10                                                   Diisopropylisosorbide             10                                          Dibutylisosorbide                     10                                      ______________________________________                                    

Nonabrasive gels are prepared by blending active isosorbide actives inamounts shown above with peppermint and clove oils. This blend is addedto a mixture of water, sodium lauryl sulfate, saccharin and sodiumbenzoate. To this is added cellulose polymer thickener until a smoothgel forms. Add additional water to adjust active concentration, allowbulk to sit for 24 hours and place in suitable containters. Fluoridesmay be added to this system. The gels appear to be very effectivewithout added detergent. Gel viscosity can be adjusted by reducing orincreasing thickened concentration.

Throat and mouth treatments with the compounds of Formula I may becarried out in blends with soft candy substances in the form ofnonconsumable material such as chewing gun and bubble gum or as aconsumable confection such as taffy, caramels, gumdrops, etc. Theseitems provide an excellent way of treating the teeth and gums especiallywhere plaque and calculus formation is greatest.

A chewing gum formula normally comprises a gum base, sweetener,plasticizer and Formula I compound. Chewing gum base is a blend ofsynthetic and natural products coming within the Food, Drug and CosmeticLaw 21 CFR 121.1054. It contains masticatory substances such as natural(coagulated or concentrated) lattices of vegetable origin, e.g., Chicle,Perillo and natural rubber to name a few. Synthetic lattices such asbutadiene-sytrene rubber, butyl rubber, paraffin, polyvinylacetate,polyvinylethylene, blends of these and others may also be used. Furthermaterials which may be included are plasticizing materials such asglycerol esters of rosin, terpine resins and antioxidants such asbutylated hydroxy anisol. The chewing gums may also contain coloringagents, pigments, flavor and sweeteners both artificial and natural asnamed above.

EXAMPLE 65 Chewing gum

    ______________________________________                                        Ingredients         % By Wt.                                                  ______________________________________                                        Gum base            25                                                        70% Sorbitol/water solution                                                                       11                                                        Dimethylisosorbide  10                                                        Crystalline Sorbitol NF                                                                           53                                                        Glycerine NF        0.5                                                       Flavor              q.s.                                                      ______________________________________                                    

The gum base was mixed in a small mixer and heated in a water bath at38° C. After mixing for four minutes, flavoring was added and mixing wascontinued for 2 minutes. The mixture was heated to 43° and cast intosticks on a flat plate.

Suitable gums may also be prepared using sugar in place of the sorbitolsolution. It is recognized, however, that a chewing gum free of sugarprovides a poorer environment for the formation of dental plaque.

Edible gums comprises any of a number of colloidal polysaccharidesubstances of plant origin that are gelatinous when moist but hard whendry, for example, gum arabic.

Taffy, nougats and caramels are derived from boiled sugars such asmolasses and brown sugar which are pulled to incorporate air and castinto blocks; these may also incorporate conventional fruit flavors, orchocolate or vanilla. The dianhydrohexitol ethers of Formula I may beincorporated with masticatory substances at any convenient point ofmanufacture in concentrations ranging from 5-25% by weight in regularformulations.

EXAMPLE 66 Nougat

    ______________________________________                                        Ingredients        (Parts by Wt.)                                             ______________________________________                                        Corn syrup         5                                                          Honey              10                                                         Dried egg albumen  1                                                          Water              4                                                          II                                                                            Sugar              40                                                         Corn syrup         30                                                         Water              10                                                         III                                                                           Vanilla flavoring  .18                                                        Hard vegetable butter 92° C.                                                              3.0                                                        Nuts               12.0                                                       Dimethylisosorbide 11.5-22.5                                                  ______________________________________                                    

Part I is made by dissolving egg albumen in the specified amount ofwater and cooking the honey and corn syrup to 116° C. Place in bowl ofmixer and heat to at least 71° C. Slowly add dissolved egg albumen. Beatuntil batch is light and fluffy.

To manufacture Part II, cook sugar and syrup to 130° C. Add the sugarand syrup mixture slowly to the beaten egg white mixture. Continuebeating until batch begins to stiffen.

To manufacture Part III, add together in the order named dimethylisosorbide, flavoring, melted hard butter and nuts. After mixing butterand nuts into batch, pour into trays that have been dusted with starchand lined with edible wafer paper. Pour at least three centimeters deep.Cover the top of the batch with wafer paper. Let set for two days toripen. Take solidified material out of the trays and cut into blocksabout 2 centimeters square. Wrap in wax paper or moisture proofcellulose wrappers.

About 2.5-10% based on the total formula weight of the Formula Iingredients could be added for taffy and marshmallow.

EXAMPLE 67 Chewable Tablet

    ______________________________________                                        Ingredients       Per Tablet (mg.)                                            ______________________________________                                        Dimethylisosorbide                                                                              20                                                          Wintergreen oil   0.6                                                         Menthol           0.85                                                        Peppermint oil    0.3                                                         Silica (Syloid 244)                                                                             1.0                                                         Sodium saccharin  0.3                                                         Sodium bicarbonate                                                                              14.0                                                        Mannitol, USP (Granular)                                                                        160.95                                                      Calcium stearate  2.0                                                         ______________________________________                                    

Mix dimethylisosorbide, flavoring oils and menthol to form a clearliquid. Absorb the mixture on silica and added the remainingingredients. Blend and compress the mixture on 1 centimeter flat bevelededge punch to a thickness of about 3.1 millimeters.

EXAMPLE 68 Sugarless Hard Candy

    ______________________________________                                        Ingredients          % By Wt.                                                 ______________________________________                                        70% Sorbitol in aqueous solution                                                                   86-99                                                    Dimethylisosorbide   10                                                       citric acid          0.5-1.5                                                  Crystalline Sorbitol Seed grade                                                                    .5                                                       Flavoring            .2-1                                                     Color                q.s.                                                     ______________________________________                                    

Weigh out the appropriate amount of sorbitol solution and transfer it toa cooking vessel. Avoid scorching the batch causing yellowing of thesolution. Begin cooking it using low heat until the sorbitol solutionhas been warmed to 70° C. Then apply sufficient heat to heat thesolution to 163° C., at which point the moisture is approximately 3.0%.

Cool the cooked batch evenly and with agitation using the tempered waterat about 65°-70° C. which is circulating in a jacket placed around thecooking vessel. If anhydrous citric acid is used add it to the batchwhile cooling when the temperature is about 140°-146° C. Hold the batchat this temperature until all the crystals have melted. Continue to coolthe batch to 87° C. It is important that (a) the batch not besupercooled by using cold water to lower the batch temperature with goodagitation; and (b) agitation be kept to a minimum to avoid entrapment oflarge quantities of air which will ruin clarity.

After the batch is cooled to 88° C., add 0.5% crystalline sorbitol seedgrade slowly to the batch while mixing thoroughly with slow agitation.The seed will nucleate the melt. Once the seed is added, check the melttemperature and adjust the temperature to 88° plus or minus 1° C., beingcareful not to overheat the melt above 92° C., destroying the seedcrystal. Coloring and flavoring are then added to the melt. Any otheroptional ingredients may be added at this point or if they are heatstable added to the melt while it is being cooled to between 135° and115° C. During this cool down period the dimethylisosorbide is blendedin. The melt should then be deposited into molds which have been broughtto room temperature to avoid super cooling. Melts deposited into moldswhich have been chilled even 2°-3° C. below room temperature will takelonger to set up. Once deposited, if the mold is maintained in an areawith a temperature of 24°-27° C. and a relative humidity of 40-45%, thecandy should be ready to demold in 20-30 minutes depending on the size,shape and type of mold used.

By allowing the hard candy to dissolve slowly in the mouth, a tinglingmouthfeel takes place indicative of mouthwash and toothpaste aspreviously described. Frequent use of the candy will act to inhibitplaque formation in the same way as does the toothpaste and mouthwash.

As a further extension of this invention, it is possible and desirableto blend healing agents with the tetraether derivatives of Formula I inmouthwashes and toothpaste to stimulate healthy normal tissue formation.A demulcent healing agent found to be compatible with the tetraetherderivatives of Formula I is Allantoin (glyoxyl-diureide)5-ureidohydantoin a well known material sometimes prepared by theoxidation of uric acid. It is expected that when used in therapeuticconcentrations of 0.12% by weight in dentifrices Allantoin will act topromote the healing of gum tissue.

EXAMPLES 69-71 Allantoin Tooth Cleaning Drops

    ______________________________________                                                      % By Weight                                                     Ingredients     #69        #70    #71                                         ______________________________________                                        Allantoin       0.2        0.5    0.1                                         Dimethylisosorbide                                                                            10.0       25.0   10.0                                        Peppermint Oil NF                                                                             1.5        1.5    1.5                                         Clove Oil NF    0.3        0.3    0.3                                         Sodium Saccharine NF                                                                          0.2        0.2    0.2                                         Sodium Benzoate NF                                                                            0.2        0.2    0.2                                         Water (distilled) q.s.                                                        ______________________________________                                    

Tooth cleaning drops are prepared by first dissolving Allantoin and theflavoring agents in dimethylisosorbide, second dissolving the sodiumsalts in half the required water, third mixing the two solutionstogether and fourth adding water to full volume by weight. The sameprocedure is followed for all formulations.

EXAMPLES 72-73 Allantoin Toothpaste Gel

    ______________________________________                                                          % By Weight                                                 Ingredients         #72    #73                                                ______________________________________                                        Dimethylisosorbide  10     25                                                 Allantoin           .02    0.5                                                Peppermint Oil NF   1.5    1.5                                                Clove Oil NF        0.3    0.3                                                Sodium Saccharine NF                                                                              0.2    0.2                                                Sodium Benzoate NF  0.2    0.2                                                Klucel ® MF Thickener                                                                         2.5    2.5                                                (Cellulose polymer)                                                           Sodium Lauryl Sulfate                                                                             1.5    1.5                                                Water (distilled) q.s.                                                        ______________________________________                                    

Mix Allantoin, dimethylisosorbide, peppermint oil and clove oil.Dissolve sodium lauryl sulfate, saccharine, and sodium benzoate inwater. Mix the two solutions well and add Klucel®MF. Continue mixinguntil a smooth gel forms. Dilute the mixture to full volume with waterand allow the bulk material to sit 24 hours. Fill suitable containersfor storage.

Another embodiment of the invention pertains to coating dental flosswith the tetraethers derivatives of Formula I. The dental profession hasrecognized the value of daily flossing between the teeth to clean outdental plaque and food debris. Coating dental floss with a therapeuticamount of a compound of Formuls I such as dimethylisosorbide willprovide a method for making intimate contact between the teeth tocapitalize on the solvent properties of the ether to wash away any boundforeign materials especially dental plaque.

EXAMPLES 74-76 Dental Floss

    ______________________________________                                                       % By Weight                                                    Ingredients      #74       #75    #76                                         ______________________________________                                        Dimethylisosorbide                                                                             25        50     75                                          Sodium Lauryl Sulfate NF                                                                       1.5       1.5    1.5                                         Peppermint Oil NF                                                                              1.5       1.5    1.5                                         Clove Oil NF     0.3       0.3    0.3                                         Sodium Saccharine NF                                                                           0.2       0.2    0.2                                         Sodium Benzoate NF                                                                             0.2       0.2    0.2                                         Water (distilled) q.s.                                                        ______________________________________                                    

First mix the dimethylisosorbide and flavorings. Then dissolve thesodium lauryl sulfate, saccharine and benzoate in water. Mix the twosolutions.

Pass the dental floss fiber through this solution into a suitable spooland package in a water tight closure. The floss should be used in theusual manner.

It has been shown that antigenic protein present on the cell walls andin cultures of Streptococcus mutans especially genetic group I (cyrotypes, c, e, and f) when separated from other antigenic proteins give anantigenic portion which may be used as a vaccine or to raise antibodiesfor use in protecting against dental caries in monkeys as demonstratedin U.S. Pat. No. 4,448,768. These antigenic materials are proteincompounds remaining on the cell walls of Streptococcus mutans afterextraction of the cell with sodium dodecyl sulfate in water for one hourat room temperature. They have a molecular weight of about 29,000±3,000.These may be administered to man or other mammals in doses of 1-50micrograms per kilogram body weight to reduce the formation of dentalcaries in the immunized subject.

The dianhydrohexitol ethers used in the invention are effective incontrolling plaque formation on the teeth by a method not clearlyunderstood. However, accepting the fact that S. mutans as demonstratedabove are responsible for the formation of caries in a sugarenvironment, a demonstration that the compositions of Formula I inhibitthe activities of S. mutans would provide presumptive evidence for theabove described theory.

A study was designed to determine the effectiveness of selectedaliphatic ethers of formula I as antimicrobial agents.

In one series of experiments the plaque producing microbe, Streptococcusmutans ATCC 27351 was grown in Brain-Heart Infusion Broth overnight (18hours), at 37° C. Seven ten-milliliter aliquots were removed from thewell agitated culture and used as an inoculum for each of the testreaction vessels. (Control, DMI, DEI, DIPI each at, 10 and 15%). Thereaction vessels were water jacketed glass spinner flasks and weremaintained at 37° C. by a circulating water bath. In this instance thechemicals to be tested were added within minutes of the inoculum.Microbial population data is tabulated in Table VIII.

In a second phase of this study Streptococus mutans was given an 18 hour"head start", i.e., the potential antimicrobial agents were added 18hours after the inoculation of the reaction vessels. In each of thephases the microbial population (colony count) was monitored at 1, 3.5,7.0, 22, 26, 46, 50, 70, 74, 94, and 98 hours. In phase two of the studyDMI, DEI, DIPI, were tested at concentrations of 0 (Control), 1, 5, 10and 15%.

                                      TABLE VIII                                  __________________________________________________________________________    REACTION VESSEL INOCULATED WITH STREPTOCOCCUS MUTANS                          FOLLOWED IMMEDIATELY BY CANDIDATE ANTIMICROBIAL                               __________________________________________________________________________               MICROBIAL POPULATION AFTER INOCULATION                                           0     3.5                                                                              7.0  22   26    46 Hrs.                                __________________________________________________________________________    Control    -- 1 × 10.sup.1                                                                  <10                                                                              1 × 10.sup.1                                                                 1.7 × 10.sup.5                                                               8.5 × 10.sup.6                                                                1.0 × 10.sup.7                   Dimethylisosorbide                                                                       10%                                                                              <10   <10                                                                              <10  <10  <10   <10                                    Dimethylisosorbide                                                                       15%                                                                              <10   <10                                                                              <10  <10  <10   <10                                    Diethylisosorbide                                                                        10%                                                                              <10   <10                                                                              <10  <10  <10   <10                                    Diethylisosorbide                                                                        15%                                                                              <10   <10                                                                              <10  <10  <10   <10                                    Diisopropylisosorbide                                                                    10%                                                                              <10   <10                                                                              <10  <10  <10   <10                                    Diisopropylisosorbide                                                                    15%                                                                              <10   <10                                                                              <10  <10  <10   <10                                    __________________________________________________________________________               MICROBIAL POPULATION AFTER INOCULATION                                           50   70   74   94   98   118 Hrs.                               __________________________________________________________________________    Control    -- 2.0 × 10.sup.7                                                               7.5 × 10.sup.5                                                               2.0 × 10.sup.6                                                               1.0 ×  10.sup.5                                                              7.0 × 10.sup.5                                                               5 × 10.sup.5                     Dimethylisosorbide                                                                       10%                                                                              <10  <10  <10  <10  <10  <10                                    Dimethylisosorbide                                                                       15%                                                                              <10  <10  <10  <10  <10  <10                                    Diethylisosorbide                                                                        10%                                                                              <10  <10  <10  <10  <10  <10                                    Diethylisosorbide                                                                        15%                                                                              <10  <10  <10  <10  <10  <10                                    Diisopropylisosorbide                                                                    10%                                                                              <10  <10  <10  <10  <10  <10                                    Diisopropylisosorbide                                                                    15%                                                                              <10  <10  <10  <10  <10  <10                                    __________________________________________________________________________

                                      TABLE IX                                    __________________________________________________________________________    ANTIMICROBIAL* PROPERTIES OF VARIOUS ETHERS OF ISOSORBIDE                     __________________________________________________________________________                  0    1.0  3.5  7.0  22   26 Hrs.                                __________________________________________________________________________    Control       3.2 × 10.sup.8                                                               3.3 × 10.sup.8                                                               3.3 × 10.sup.8                                                               3.2 × 10.sup.8                                                               2.3 × 10.sup.8                                                               --                                     Dimethylisosorbide                                                                        1%                                                                              --   1.8 × 10.sup.8                                                               2.0 × 10.sup.8                                                               3.0 × 10.sup.8                                                               9.3 × 10.sup.7                                                               --                                                 5%                                                                              --   1.4 × 10.sup.8                                                               1.3 × 10.sup.8                                                               1.5 × 10.sup.8                                                               1.0 × 10.sup.8                                                               --                                                10%                                                                              9.2 × 10.sup.7                                                               --   9.2 × 10.sup.7                                                               9.0 × 10.sup.7                                                               3.1 × 10.sup.6                                                               6.3 × 10.sup.6                              15%                                                                              1.1 × 10.sup.8                                                               --   7.6 × 10.sup.7                                                               2.7 × 10.sup.7                                                               1.1 × 10.sup.4                                                               1.4 × 10.sup.3                   Diethylisosorbide                                                                         1%                                                                              --   1.6 × 10.sup.8                                                               2.0 × 10.sup.8                                                               3.1 × 10.sup.8                                                               9.7 × 10.sup.7                                                               --                                                  5%                                                                             --   1.3 × 10.sup.8                                                               9.9 × 10.sup.7                                                               9.2 × 10.sup.7                                                               6.6 × 10.sup.7                                                               --                                                10%                                                                              --   --   --   --   --   --                                                15%                                                                              2.4 × 10.sup.8                                                               --   8.6 × 10.sup.7                                                               <10  <10  <10                                    Diisopropylisosorbide                                                                     1%                                                                              --   1.3 × 10.sup.8                                                               1.3 × 10.sup.8                                                               1.1 × 10.sup.8                                                               9.6 × 10.sup.7                                                               --                                                 5%                                                                              --   1.3 × 10.sup.8                                                               9.9 × 10.sup.7                                                               9.2 × 10.sup.7                                                               6.6 × 10.sup.7                                                               --                                                10%                                                                              --   --   --   --   --   --                                                15%                                                                              1.1 × 10.sup.8                                                               --   9.2 × 10                                                                     <10  <10  <10                                    __________________________________________________________________________                  46   50   70   74   94   98 Hrs.                                __________________________________________________________________________    Control       1.3 × 10.sup.8                                                               1.8 × 10.sup.8                                                               1.5 × 10.sup.8                                                               1.4 × 10.sup.8                                                               6.1 × 10.sup.7                                                               5.7 × 10.sup.7                   Dimethylisosorbide                                                                       1% 1.6 × 10.sup.8                                                               3.0 × 10.sup.7                                                               9.9 × 10.sup.7                                                               1.2 × 10.sup.8                                                               3.7 × 10.sup.8                                                               3.0 × 10.sup.8                              5% 1.2 × 10.sup.8                                                               1.3 × 10.sup.8                                                               1.4 × 10.sup.8                                                               1.2 × 10.sup.8                                                               8.5 × 10.sup.7                                                               8.6 × 10.sup.7                              10%                                                                              8.2 × 10.sup.4                                                               8.1 × 10.sup.4                                                               2.0 × 10.sup.3                                                               1.1 × 10.sup.3                                                               <10  <10                                               15%                                                                              <10  <10  <10  <10  <10  <10                                    Diethylisosorbide                                                                        1% 1.2 × 10.sup.8                                                               2.1 × 10.sup.8                                                               1.8 × 10.sup.8                                                               1.6 × 10.sup.8                                                               1.0 × 10.sup.8                                                               9.7 × 10.sup.7                              5% 5.7 × 10.sup.7                                                               5.8 × 10.sup.7                                                               2.4 × 10.sup.8                                                               1.9 × 10.sup.8                                                               1.3 × 10.sup.8                                                               1.2 × 10.sup.8                              10%                                                                              --   --   --   --   --   --                                                15%                                                                              <10  <10  <10  <10  <10  <10                                    Diisopropylisosorbide                                                                    1% 2.9 × 10.sup.8                                                               4.8 × 10.sup.8                                                               4.3 × 10.sup.8                                                               2.9 × 10.sup.8                                                               2.5 × 10.sup.8                                                               2.4 × 10.sup.7                              5% 5.7 × 10.sup.7                                                               5.8 × 10.sup.7                                                               2.4 × 10.sup.8                                                               1.9 × 10.sup.8                                                               1.3 × 10.sup.8                                                               1.2 × 10.sup.8                              10%                                                                              --   --   --   --   --   --                                                15%                                                                              <10  <10  <10  <10  <10  <10                                    __________________________________________________________________________     *Approximately 18 hours was allowed between inoculation and antimicrobial     addition.                                                                

Both experiements give an indication that the population of S. mutans isdrastically reduced in the environment of the dianhydrohexitolderivatives employed in the treatment method and compositions of theinvention.

Dissolution studies were carried out with dimethylisosorbide onharvested human dental calculus (tartar) that was collected and held innormal saline solution until ready for testing. The calculus was addedto 100% dimethylisosorbide as well as 50/50 solution ofdimethylisosorbide/water and allowed to sit in a resting position withoccasional stirring. The calculus slowly dissolved into thedimethylisosorbide over a 24-hour period (200 mg. in 100 ml. ofsolvent). This occurred in both solutions.

In another dissolution study extracted soiled human teeth were immersedin 100% dimethylisosorbide as well as a 50/50 solution ofdimethylisosorbide/water. These solutions were stirred occasionally andobserved for changes in appearance over a several week period. It wasnoted in particular that the part of the tooth that is exposed above thegum line, self-cleaned and became very clean and white after 24 to 36hours. The bottom of the beaker became loaded with debris. It was alsoobserved that dimethylisosorbide did not dissolve or loosen the fillingsin the teeth. Each dilution appeared to be equally effective.

What is claimed is:
 1. A method for inhibiting the formation of plaqueand calculus in the oral cavity of mammals which comprises periodicallytreating the surfaces of the teeth and gums with a toothpaste gelcontaining an S. mutans inhibiting amount of a dianhydrohexitol compoundhaving the general formula: ##STR2## wherein R' and R" are individuallyselected from alkyl radicals selected from the group consisting of--CH₃, --C₂ H₅, --C₃ H₇, --C₄ H₉ or --H when the other R' or R" is analkyl radical of 1-4 carbon atoms whereby at least a portion of thebacteria on said surfaces is essentially inhibited from further growthor removed by dissolution.
 2. A method of claim 1 wherein saiddianhydrohexitol is selected from the group consisting ofmethylisosorbide, dimethylisosorbide, ethylisosorbide,diethylisosorbide, isopropylisosorbide, diisopropylisosorbide,butylisosorbide, dibutylisosorbide, methylethylisosorbide,methylpropylisosorbide, methylbutylisosorbide, ethylpropylisosorbide andethylbutylisosorbide.
 3. A method of claim 1 wherein saiddianhydrohexitol is dimethylisosorbide.
 4. In a toothpaste gelformulation for treating the teeth and gums which comprises at least twoingredients selected from the group consisting of water, solids,stabilizers, coloring agents, flavoring agents, surfactants,astringents, detergents, polishing agents, thickeners and pigments, theimprovement which consists essentially of including therewith an Smutans inhibiting amount of a dianhydrohexitol compound having thegeneral formula: ##STR3## wherein R' and R" are individually selectedfrom alkyl radicals selected from the group consisting of --CH₃, --C₂H₅, --C₃ H₇, --C₄ H₉ or --H when the other R' or R" is an alkyl radicalof 1-4 carbon atoms.
 5. A toothpaste gel of claim 4 containing 5-95% byweight of said dianhydrohexitol.
 6. A toothpaste gel of claim 4 whereinsaid dianhydrohexitol is selected from the group consisting ofmethylisosorbide, dimethylisosorbide, ethylisosorbide,diethylisosorbide, isopropylisosorbide, diisopropylisosorbide,butylisosorbide, dibutylisosorbide, methylethylisosorbide,methylpropylisosorbide, methylbutylisosorbide, ethylpropylisosorbide andethylbutylisosorbide.
 7. A toothpaste gel composition of claim 4containing 10-50% by weight dimethylisosorbide.
 8. A toothpaste gelcomposition of claim 4 containing from 0.02-0.5% by weight allantoin.